• IMMUNE NETWORK
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• v.21 no.3
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• pp.22.1-22.17
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• 2021

Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells. K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.

• Journal of Acupuncture Research
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• v.23 no.6
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• pp.103-115
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• 2006

Objectives : Rheumatoid arthritis(RA) is a systemic & a chronic inflammatory autoimmune disease . A chronic , locally destructive inflammmatory reaction in human is examplified by the synovitis present in some connective tissue disorder. The presence of a number of cytokines, $TNF-{\alpha}$, iNOS & expression of nitric oxide, NF-kB p65 activation implies an important role of cellular immune response in RA inflammatory reaction. This study was designed to evaluate on the effects of the Homnis Placenta herbal acupuncture on EX-LE201 & ST 35 reducing expression of LPS-induced arthritis model in mice. Materials and Methods : Homnis Placenta herbal acupuncture was inserted into 10 rats induced rheumatoid arthritis. The acupunctures were injected into the EX-LE201 and ST35 points. Such indexes were measured the inhibition of inducible nitric oxide synthase(iNOS) expression, nitric oxide(NO) production in vitro experiment and Tumor Necrosis $Factor-{\alpha}(TNF-{\alpha})$ & Nuclear Factor kappa $B(NF-{\kappa}B)$ p65 activation, synovial hyperplasia, angiogenesis and fibrosis in synovial membrane of knee joint of mice in vivo experiment. Results : 1.Homnis Placenta Herbal acupuncture inhibited iNOS mRNA and NO in RAW 264.7 cell of LPS-induced rheumatoid arthritis in a dose dependent manner. 2.Homnis Placenta Herbal acupuncture also showed significant inhibition of $TNF-{\alpha}$ & $NF-{\kappa}B$ p65, activation, synovial hyperplasia, angiogenesis and fibrosis in synovial membrane of knee joint of mice. Conclusion : These results suggest that Homnis Placenta Herbal acupuncture has an therapeutic effects on LPS induced-rheumatoid arthritis by inhibiting $TNF-{\alpha}$ activation.

• Preventive Nutrition and Food Science
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• v.20 no.2
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• pp.83-87
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• 2015

Omega-3, a polyunsaturated fatty acid, is an essential fatty acid necessary for human health, and it protects against cardiovascular disease, inflammation, autoimmune diseases, and cancer. In the present study, we investigated the effects of omega-3-rich harp seal oil (HSO) on the production of nitric oxide (NO) and cytokines, such as tumor necrosis factor (TNF)-${\alpha}$, interleukin-(IL)-$1{\beta}$, IL-6, and IL-12/IL-23 (p40) in peritoneal macrophages of mice. The culture supernatants of murine macrophages exposed to lipopolysaccharide (LPS), HSO, or HSO+LPS were harvested to assay IL-$1{\beta}$, TNF-${\alpha}$, IL-6, and IL-12/IL-23 (p40) cytokines and NO. TNF-${\alpha}$, IL-$1{\beta}$, and IL-12/IL-23 (p40) levels, except IL-6, were lower in the culture supernatants of mouse peritoneal macrophages exposed to LPS plus HSO than those of the groups exposed to LPS alone. These observations demonstrate that omega-3-rich harp seal oil downregulates the production of the pro-inflammatory cytokines such as IL-$1{\beta}$, TNF-${\alpha}$, and IL-12/IL-23 (p40). These results suggest that HSO could be potentially used as a preventive agent or as an adjunct in anti-inflammatory therapy, if more research results were accumulated.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1423-1430
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• 2009

Rosmarinic acid frequently found as a secondary metabolite in herbs and medicinal plants, has exhibited antimicrobial, antiviral, antioxidative, and anti-inflammatory activities. The proliferation and migration of human aortic smooth muscle cells (HASMC) in response to activation by various stimuli plays a critical role in the initiation and development of atherosclerosis. This study was conducted to examine the effects of Rosmarinic acid on the proliferation and migration of HASMC. Rosmarinic acid suppressed the proliferation of HASMC via induction of the expression of apoptotic proteins including cleaved poly ADP-ribose polymerase (PARP), and caspase-3. Rosmarinic acid decreased anti-apoptotic Bcl-2 and increased pro-apoptotic Bax. Moreover, treatment of rosmarinic acid decreased the G1/S cycle regulation proteins (cyclin D1, cyclin E, CDK2, CDK4 and CDK6) and increased p21, p27 and p53. Rosmarinic acid also blocked HASMC migration via suppression of MMP-9 and MMP-2. Taken together, these results indicate that rosmarinic acid has the potential for use as an anti-atherosclerosis agent.

• The Korea Journal of Herbology
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• v.29 no.1
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• pp.53-60
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• 2014

Objectives : Bojungikgitang (BJT), the Oriental medical prescription has been traditionally used about improvement of immune response and infective disease at Asian nation. In this study, we has compared about the anti-inflammatory and antioxidative effects on BJT of three countries including Korea (Korean Traditional Medicine, KTM), China (Traditional Chinese Medicine, CTM) and Japan (Japanese Traditional Medicine, JTM). Methods : We has basically using LPS-stimulated RAW 264.7 cells. The expression of these inflammatory mediators has measured using enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). Also, free radical scavenging assay has tested for anti-oxidative activity as well as the contents of total flavonoid and polyphenol. Results : As a result, we were founded the inhibitory effects of BJT (KTM, CTM, JTM) on LPS-induced production of NO, TNF-${\alpha}$ and IL-6 as well as the anti-oxidative activities. Especially the KTM was most effective in anti-inflammatory and anti-oxidative activities. Conclusions : These results indicate that BJT (KTM, CTM, JTM) has a good anti- inflammatory and anti-oxidative effects. But, there were degree of effects on between pharmacopoeia of the countries. Thus, further study is required that find appropriate methods for extracting as well as establish of standardized processes in order to improve the quality of BJT (KTM, CTM, JTM) as an anti-inflammatory and anti-oxidative agent for treatment of inflammatory diseases.

• IMMUNE NETWORK
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• v.12 no.5
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• pp.181-188
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• 2012

Dioscoreae Rhizome (DR) has been used in traditional medicine to treat numerous diseases and is reported to have anti-diabetes and anti-tumor activities. To identify a bioactive traditional medicine with anti-inflammatory activity of a water extract of DR (EDR), we determined the mRNA and protein levels of proinflammatory cytokines in macrophages through RT-PCR and western blot analysis and performed a FACS analysis for measuring surface molecules. EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and $PGE_2$, as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 was also reduced by EDR. Furthermore, activation of the nuclear transcription factor, NF-${\kappa}B$, but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. These results show that EDR decreased pro-inflammatory cytokines via inhibition of NF-${\kappa}B$-dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.4
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• pp.226-231
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• 2018

Chijabaegpi-tang (CHG) is an oriental herbal medicine that has been used for its various pharmacological effects, which include anti-inflammatory, anti-oxidant and immunoregulation activities. In the present study, we investigated which skin inflammations are involved in the $TNF-{\alpha}/IFN{\gamma}$-induced HaCaT cells. We investigated the suppressive effect of CHG on $TNF-{\alpha}/IFN{\gamma}$-induced HaCaT cell production of the following chemokines: macrophage-derived chemokine (MDC)/CCL22; regulated on activation, normal T-cell expressed and secreted (RANTES)/CCL5; and interleukin-8 (IL-8); thymus and activation-regulated chemokine (TARC)/CCL17. The pre-treatment of HaCaT cells with CHG suppressed $TNF-{\alpha}/IFN{\gamma}$-induced nuclear transcription factor kappa-B ($NF-{\kappa}B$). In addition, CHG inhibited $TNF-{\alpha}/IFN{\gamma}$-induced phosphorylation of ERK and p38. $TNF-{\alpha}/IFN{\gamma}$ suppressed the expression of skin barrier proteins, including filaggrin (FLG), Involucrin (IVL) and loricrin (LOR). By contrast, CHG restored the expression of FLG, IVL and LOR. Taken together, our findings suggest that CHG could be a therapeutic agent for prevention of skin disease, including atopic dermatitis.

• The Korea Journal of Herbology
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• v.22 no.4
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• pp.117-125
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• 2007

Objectives : Berberine, a main alkaloid component of Coptidis rhizoma, has an antimicrobial and anti-tumor activities and antiinflammatory effect. In the present study, we investigated effect of berberine on the production of inflammatory mediators such as nitric oxide(NO), prostaglandin E2(PGE2), TNF-${\alpha}$ and IL-1${\beta}$ in LPS-stimulated BV2 microglial cells, Methods : BV2 cells were pre-treated with berberine and then stimulated with LPS. The cytotoxicity of berberine was determined by MTT assay. The NO production was measured by Griess assay. The mRNA expression and protein levels of inducible nirtic oxide synthase(iNOS) were determined by RT-PCR and Western blot. The production of PGE2 and cytokines was measured by ELISA. Results : Berberine inhibited the production of NO, PGE2 and pro inflammatory cytokines, TNF-${\alpha}$ and IL-1${\beta}$ in a dose dependent manner in LPS-stimulated BV2 cells. In addition, berebrine greatly suppressed the mRNA expression and protein levels of iNOS and inflammatory cytokines induced by LPS stimulation. These results indicate that the post-transcriptional regulatory mechanism of iNOS and/or inflammatory cytokine gene expression by berberine is involved in its anti-inflammatory effects, respectively. Conclusion : The present study suggests that berberine can be useful as a potential anti-inflammatory agent for treatment of various neurodegenerative diseases such as Alsheimer's disease, Parkinson's disease and stroke.

• The Journal of Korean Medicine
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• v.29 no.2
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• pp.81-95
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• 2008

Objectives: Whitmania pigra whitman (WP) has been used in herbal medicine to treat various conditions, such as eczema, skin burns and frostbites in herbal medicine. The purpose of this study is was to investigate the effect of WP on anti-allergy mechanism. Methods: To clarify the mechanism, the effect of WP on vascular permeability of rat cutaneous tissue and histamine and cytokines (IL-6, IL-8, $TNF-{\alpha}$) released from mast cells were observed. Results: The results were 1. the pretreatment with WP significantly decreased the compound 48/80-induced degranulation and histamine release from RPMC 2. WP did not inhibit the anti-DNP IgE-induced increment of vascular permeability of rat cutaneous tissue 3. WP significantly reduced the PMA plus A23187-induced increment of expression of IL-6, IL-8, and $TNF-{\alpha}$ in HMC-1 cells. Conclusions: The present study providesevidence that WP acid inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression, and suggest the mechanisms of action. Furthermore, in vivo and in vitro anti-allergic effect of WP suggests a possible therapeutic application of this agent in inflammatory allergic diseases.

• The Korea Journal of Herbology
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• v.31 no.5
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• pp.79-84
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• 2016

Objective : Nypa fruticans Wurmb. Fruit (NF) has been used as a conventional medicine to treat inflammatory peridontal diseases in Myanmar and Eastern Asia. However, the anti-inflammatory effect of NF aqueous extract on lipopolysaccharide (LPS)-induced inflammatory responses was not well-investigated. Therefore, this study was aimed to investigate the anti-inflammatory effect of NF on LPS-induced inflammatory responses on RAW 264.7 cells.Methods : To induce inflammation on the macrophage cell line, RAW 264.7 cells were treated with 500 ng/mL of LPS. Water extracts of NF was treated 1 h prior to treatment of LPS. Cell viability was measured by MTT assay. Production of nitrite was measured with Griess assay and pro-inflammatory cytokines such as interleukine (IL)-1β and IL-6, and tumor necrosis factor (TNF)-α was measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). In addition, we examined the inhibitory mechanisms of NF by western blot and immunocytochemistry.Result : Water Extract from NF itself did not have any cytotoxic effect at the concentration of 200 ㎍/ml in RAW 264.7 cells. Treatment of NF inhibited the production of nitrite, and pro-inflammatory cytokines inlcuding IL-1β, IL-6 and TNF-α in a dose dependant. In addition, NF treatment inhibited the LPS-induced activation and translocation of nuclear factor (NF)-κB.Conclusion : In summary, our result suggest that treatment of NF could reduce the LPS-induced inflammatory responses via deactivation of NF-κB. This study could suggest that NF could be a beneficial drug or agent to prevent inflammation.